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Lipid metabolism mind map
This is a mind map about lipid metabolism, including the function and analysis of the composition of lipids, the digestion and absorption of lipids, etc.
Edited at 2023-11-16 17:37:30
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fat metabolisim
Plasma lipoproteins and their metabolism
Blood lipids are the collective name for the lipids contained in plasma
include
Triglycerides, phospholipids, cholesterol and its esters, free fatty acids
source
external source
food
endogenous
Liver cells, adipocytes and other tissue cells
way out
Oxidative decomposition provides energy
Enter lipid storage
constitute biofilm
transform into other substances
Features
Large fluctuation range
Plasma lipoproteins are the transport and metabolic forms of blood lipids
plasma lipoproteins
Include
protein
apolipoprotein
Lipids
Triglycerides
Phospholipids
cholesterol
cholesterol ester
Free fatty acids (FFA) are bound to albumin and transported
structure
spherical
Apolipoproteins, phospholipids, and cholesterol have polar ends outside
Contains hydrophobic triglycerides and cholesterol esters
Function
Binds and transports lipids, stabilizing lipoprotein structure
Can participate in the recognition of lipoprotein receptors
Regulates the activity of key enzymes in lipoprotein metabolism
Separation method
electrophoretic separation
Ultracentrifugation
Chylomicrons (CM)
The smallest density and the largest particles
Very low density lipoprotein (VLDL)
Low density lipoprotein (LDL)
High-density lipoprotein (HDL)
The highest density and smallest particles
Types and functions of plasma lipoproteins
ChylomicronsCM
source
(TG synthesized in the small intestine synthesizes phospholipids and cholesterol absorbed) apoB48, apoAI, apoAII, apoAIV
Function
Transport exogenous TG and cholesterol
metabolism
key enzyme
lipoprotein lipase LPL
exist
capillary surface
activator
apoCII
Function
TG→glycerol, fatty acid
very low density lipoprotein VLDL
source
The liver synthesizes (the small intestine can synthesize a small amount) TG phospholipids, cholesterol apoB100, apoE
Function
Transport of endogenous TG
metabolism
low density lipoprotein LDL
source
Transformed from VLDL
composition
Cholesterol ester apoB100
Function
Transport of endogenous cholesterol synthesized by the liver
metabolism
Pathway 1—Low-density lipoprotein receptor metabolic pathway (2/3)
Long half-life → easily modified by oxidation
Ox-LDL is an independent factor in atherosclerosis
Pathway-2 Clearance by macrophages and vascular endothelial cells in the monocyte-phagocytic system (1/3)
scavenger receptor
Metabolism 1 Metabolism 2 = 45% LDL cleared
HDL
source
Liver synthesis (can also be done in the small intestine)
CM, VLDL metabolism
Surface lipoproteins and phospholipids, nascent HDL is formed when cholesterol leaves
Function
Reverse cholesterol transport (RCT)
Cholesterol in extrahepatic tissue cells is transported to the liver through blood circulation → converted into bile acids and excreted from the body
apoCII repository
metabolism
Fat metabolism profile
Disturbance of plasma lipoprotein metabolism leading to dyslipoproteinemia
Abnormal changes in different lipoproteins cause different types of hyperlipidemia
Inherited defects in genes related to plasma lipoprotein metabolism cause dyslipoproteinemia
LDL receptor deficiency
atherosclerosis
When the vascular endothelium is damaged, oxidized LDL will be deposited in the intima of the arterial wall and engulfed by macrophages and scavenger receptors of smooth muscle cells to form foam cells.
cholesterol metabolism
Cholesterol in the body comes from food and endogenous synthesis
Existing form
free cholesterol FC
Cholesterol Ester CE
structure
Cholesterol
Cyclopentane polyhydrophenanthrene
content
140g
distributed
Tissues throughout the body
About 1/4 is distributed in the brain and nervous tissue
More in internal organs, skin, and adipose tissue
Low muscle tissue content
Glands that synthesize steroid hormones, such as the adrenal glands and ovaries, have higher levels
source
endogenous
Self-synthesis (1g/day)
Liver, small intestine mainly
external source
Food (offal, egg yolk, butter, meat)
Daily intake does not exceed 300mg
Cholesterol in one egg: 220mg
Physiological function
Important components of biofilms
Precursors for the synthesis of bile acids, steroid hormones, vitamin D and other physiologically active substances
The main site of cholesterol synthesis in the body is the liver
synthetic parts
All tissues of the body (brain tissue, except mature red blood cells) liver (70-80%, small intestine 10%)
cytosol, smooth endoplasmic reticulum
Acetyl CoA and NADPH are the basic raw materials for cholesterol synthesis
Glucose/amino acids/fatty acids→18 acetyl CoA 36ATP 16NADPH→1 cholesterol
Acetyl CoA exits the mitochondria via the citrate-pyruvate cycle
Cholesterol synthesis is completed by a series of enzymatic reactions (about 30 steps) with HMG-CoA reductase as the key enzyme.
Synthesis of mevalonate (MVA) from acetyl CoA
Mevalonate is converted into 30C squalene via 15C compound
Squalene is cyclized to lanosterol and then converted to cholesterol
Regulation of cholesterol synthesis
HMG-CoA reductase
Activity has a diurnal pattern
High at midnight, low at noon
inhibitor
statins
allosteric adjustment
allosteric inhibitor
Cholesterol synthesis products
mevalonate, cholesterol
chemical modification regulation
Cytoplasmic cAMP-dependent protein kinase inactivates its phosphorylation
Phosphoprotein phosphatase dephosphorylates and resurrects it
Cellular cholesterol content
High content inhibits its synthesis
meal status
Starvation and fasting inhibit its synthesis
Diets high in sugar and saturated fat promote its synthesis
Hormone regulation
Insulin/Thyroxine
Promote its synthesis
Thyroxine also promotes the conversion of cholesterol into bile acids in the liver (this effect is stronger than promoting cholesterol synthesis → in hyperthyroidism, serum cholesterol decreases)
Glucagon/Cortisol
inhibit its synthesis
Metabolic transformation and excretion of cholesterol in the body
premise
The mother core - cyclopentane polyhydrophenanthrene cannot be degraded in the body, and the side chains can be oxidized, reduced or degraded
way
2/5 converted to bile acids (liver)
emulsification
Promote the absorption of lipids and inhibit the precipitation of cholesterol
Converted to 7-dehydrocholesterol (skin)
UV exposure → Vitamin D3
Converted into steroid hormones (adrenal cortex, testes, ovaries, etc.)
Phospholipid metabolism
definition
Phosphate-containing lipids
include
Glycerophospholipids
Sphingomyelin
metabolism
CTP function
provide energy
Provide carrier
CDP-Choline
CDP-cholamine
CDP-diglyceride
Lipid composition, function and analysis
Lipids are a wide variety of macromolecular substances with complex structures
Lipids
General term for fats (triglycerides) and lipids
Triglycerides are fatty acid esters of glycerol
Fatty acids are carboxylic acids of aliphatic hydrocarbons
General formula: CH3(CH2)nCOOH
Phospholipid molecules contain phosphoric acid
Cholesterol has cyclopentane polyhydrophenanthrene as its basic structure
Lipids have a variety of complex biological functions
Triglyceride (TG) is an important energy substance for the body
Large decomposition capacity (1gTG=38KJ)
Hydrophobic, does not contain water molecules during storage, and occupies a small volume
The body has specialized storage tissue—adipose tissue
Triglycerides are important stores of fatty acids
Phospholipids are important structural components and signaling molecules
Phospholipids are important components of biological membranes
Phosphatidylinositol is the precursor of the second messenger
Cholesterol is an important component of biological membranes and the precursor of sterols with important biological functions.
Cholesterol is the basic structure of cell membranes
Cholesterol can be converted into some sterol compounds with important biological functions
steroid hormones
Can be converted into bile acids in the liver
The skin converts it into vitamin D
Fatty acids have many important physiological functions
Fatty acids are important components of fats, cholesterol esters and phospholipids
Provides essential fatty acids
Fatty acids that the human body cannot synthesize by itself and must be provided by food
Linoleic acid, linolenic acid, arachidonic acid
Synthetic unsaturated fatty acid derivatives
prostaglandins, thromboxane, leukotrienes
Digestion and absorption of lipids
Bile salts assist digestive enzymes in digesting lipids
condition
Emulsifiers (bile salts, monoglycerides, diglycerides)
emulsification
Lipids→emulsified micelles
Increase the contact area between digestive enzymes and lipids to promote lipid digestion
Lipid-digesting enzyme (pancreas)
pancreatic lipase
colipase
Exists in pancreatic alveoli as zymogen
Does not have enzymatic activity itself
Is a cofactor for the action of pancreatic lipase
Phospholipase A2 (PLA2)
cholesterol esterase
parts
upper small intestine
The absorbed lipids are resynthesized and enter the blood circulation
Absorption site
Lower duodenum and upper jejunum
Triglycerides composed of short chain fatty acids
Bile salts are emulsified into emulsified micelles → taken up by intestinal mucosal cells → hydrolyzed into fatty acids and glycerol under the action of lipase → entered into the blood circulation through the portal vein.
Triglycerides composed of long-chain fatty acids Cholesterol Lysophospholipids
In the small intestinal mucosa, fatty acyl-CoA is converted → catalyzed by smooth endoplasmic reticulum fatty acyl-CoA transferase, ATP supplies energy to resynthesize triglycerides → together with carrier proteins, phospholipids and cholesterol on rough endoplasmic reticulum to form chylomicrons (CM) → After secretion by intestinal mucosal cells → Lymph capillaries → Enter blood circulation
Lipid digestion and absorption play an important role in maintaining the body's lipid balance
Small intestine—selective barrier between lipids inside and outside the body
triglyceride metabolism
break down
Oxidative decomposition of triglycerides produces large amounts of ATP
Triglyceride catabolism begins with fat mobilization
fat mobilization
The process in which fat stored in white adipocytes is gradually hydrolyzed by lipase, releasing free fatty acids and glycerol for oxidation and utilization by other tissue cells.
key enzyme
Hormone-sensitive triglyceride lipase (HSL)
trigger
Fasting/Hunger/Sympathetic Excitation
→ Increased secretion of lipolytic hormones (epinephrine, norepinephrine, glucagon) (acts on white adipocyte membrane receptors)
→Activate adenylyl cyclase
ATP→cAMP
→Activates cAMP-dependent protein kinase (PKA)
Phosphorylation of perilipin-1
Activates adipose tissue triglyceride lipase (ATGL)
Transfer phosphorylated HSL from the cytoplasm to the surface of lipid droplets
HSL phosphorylation
Fat is broken down within fat cells
first step
ATGL catalysis → diglycerides and fatty acids
Step 2
HSL catalysis →monoglycerides and fatty acids
third step
Monoglyceride lipase (MGL) catalyzes →glycerol and fatty acids
hormone
lipolytic hormone
Epinephrine, norepinephrine, glucagon
anti-lipolytic hormone
insulin
Prostaglandin E2
Glycerol is converted into glycerol 3-phosphate and used
B oxidation is the core process of fatty acid decomposition
parts
organize
Most tissues except brain (liver, muscles are most active)
subcellular
cytosol, mitochondria
process
Activation of fatty acids into fatty acyl-CoA
fatty acyl-CoA synthetase
endoplasmic reticulum, mitochondria
ATP→AMP PPi
Consumes two molecules of high-energy phosphate bonds
Pyrophosphate (PPi) is immediately hydrolyzed by pyrophosphatase
Fatty acyl-CoA enters mitochondria (rate-limiting step in fatty acid B-oxidation)
outer mitochondrial membrane
Carnitine acyltransferase I (key enzyme for fatty acid B-oxidation)
Fatty acyl-CoA carnitine → fatty acylcarnitine
inner mitochondrial membrane
carnitine acyltransferase II
Fatty acylcarnitine → Fatty acylCoA carnitine
Fatty acyl-CoA breaks down to produce acetyl-CoA, FADH2 and NADH
Fatty acid B-oxidation
Fatty acid B-oxidase system
process
Dehydrogenation of fatty acyl-CoA to enoyl-CoA
Fatty acyl-CoA dehydrogenase
FAD→FADH2
Adding water to enoyl CoA produces hydroxyacyl CoA
Hydroxyacyl-CoA is then dehydrogenated to form B-ketoacyl-CoA
NAD→NADH
Thiolysis of ketoacyl-CoA to acetyl-CoA
B-ketothiolase
Fatty acid oxidation is an important source of ATP in the body
every cycle
activation
Consumes 2 high-energy phosphate bonds
B-oxidation
1 molecule of acetyl CoA
1 molecule of fatty acylCoA with 2 less C
1 molecule NADH
1 molecule FADH2
eg: Soft fatty acid (16C)
7 round loop
8 molecules of acetyl CoA (8×10)
7NADH (7×2.5)
7FADH (7×1.5)
Net production of ATP
8×10 7×2.5 7×1.5-2 (high-energy phosphate bonds consumed) = 106ATP
Fatty acids are broken down in the liver to produce ketone bodies
include
Acetoacetate
B-Hydroxybutyric acid
acetone
process
Ketone bodies are produced in the liver
raw material
Acetyl CoA
parts
liver mitochondria
enzyme
ketone body synthase system
process
2 molecules of acetyl CoA are condensed into acetoacetyl CoA
Acetoacetyl CoA thiolase
Acetoacetyl CoA condenses with acetyl CoA to form hydroxymethylglutaryl CoA (HMG-CoA)
HMG-CoA synthase
Cleavage of HMG-CoA produces acetoacetate
HMG-CoA lyase
Acetoacetate is reduced to B-hydroxybutyrate (B-hydroxybutyrate dehydrogenase) (NADH→NAD)/a small amount of acetone
Oxidation and utilization of ketone bodies in extrahepatic tissues
B-hydroxybutyrate → acetoacetate catalyzed by B-hydroxybutyrate dehydrogenase
The utilization of acetoacetate requires activation first
Heart, kidney, brain and skeletal muscle mitochondria
Succinyl-CoA transsulfurase → acetoacetyl-CoA
Heart, kidney, brain mitochondria
Acetoacetate thiokinase → Acetoacetyl CoA
Acetoacetyl CoA is thiolyzed to form acetyl CoA
Acetoacetyl CoA thiolase
Ketone bodies are an important form of energy export from the liver to extrahepatic tissues.
Important energy source for brain tissue and muscles
Characteristics of ketone bodies
The molecule is small, soluble in water, and can pass through the blood-brain barrier and capillary walls of muscle tissue.
The brain cannot break down fatty acids but efficiently uses ketone bodies
When glucose is in sufficient supply, priority is given to glucose for energy
When glucose supply is insufficient, ketone bodies are mainly used
Ketone bodies are an alternative energy source when there is long-term hunger or insufficient sugar supply.
The increased utilization of ketone bodies can reduce the utilization of sugar, help maintain a constant blood sugar level, and save protein consumption.
Normal values of ketones in blood
0.03～0.5mmol/L
When hungry/diabetic → Increased fat mobilization → Increased ketone body production → Ketone acidosis (blood ketone bodies can be excreted in the urine if they exceed the renal threshold, causing ketonuria)
Diabetes → ketoacidosis → ketonuria
Ketone bodies are regulated by many factors
meal status
Satiation → Increased insulin secretion → Decreased fat mobilization → Decreased ketone body production
Hunger → Increased glucagon (lipolysis hormone) secretion → Increased fat mobilization → Increased ketone body production
metabolism
After meals/sugar supply is sufficient → sugar metabolism is enhanced → oxidative decomposition of fatty acids in the liver is reduced → ketone body production is inhibited
Hunger/sugar utilization disorder → Enhanced oxidation and decomposition of fatty acids, increased production of acetyl CoA (at this time, impaired glucose metabolism → decreased oxaloacetate → blocked tricarboxylic acid cycle) → massive accumulation of acetyl CoA, increased production of ketone bodies
Malonyl-CoA inhibits ketone body production
Strong glucose metabolism, increased acetyl CoA and citrate → allosteric activation of acetyl CoA carboxylase, malonyl CoA synthesis → competitive inhibition of carnitine acyltransferase I → preventing fatty acyl CoA from entering mitochondria for B oxidation → inhibiting ketones body generation
synthesis
Fatty acids from different sources synthesize triglycerides in different organs through different pathways.
Liver, adipose tissue and small intestine are the main sites for triglyceride (TG) synthesis
Subcellular localization
cytoplasm
parts
small intestinal mucosal cells
Utilizes fat digestion products to resynthesize fat
Liver (most capable of synthesis)
TG synthesized by the liver endoplasmic reticulum forms VLDL and enters the blood
Liver cells cannot store triglycerides
Very low density lipoprotein (VLDL)
composition
Triglycerides Apolipoprotein Phosphate Cholesterol
transportation
Extrahepatic tissue
VLDL generation obstacles
reason
Choline/protein deficiency
as a result of
Triglycerides accumulate in liver cells, leading to fatty liver
Adipose tissue (can be stored in large quantities - lipid depot)
Utilizing FA in CM/VLDL to synthesize fat
glucose
Glucose→dihydroxyacetone phosphate→glycerol 3-phosphate→glycerol
Glucose → Acetyl CoA → Fatty acid
way
Liver and adipose tissue cells-diglyceride pathway
raw material
3-glycerol phosphate
source
Glucose metabolism
Free glycerol in liver and kidneys
Fatty acyl-CoA
Exogenous (food digestion and absorption)
endogenous
The synthesis of endogenous fatty acids requires the synthesis of palmitic acid first
Palmitic acid is synthesized from acetyl CoA catalyzed by the fatty acid synthase complex
Subcellular localization
cytoplasm
16C Palmitic Acid
Liver mitochondria, endoplasmic reticulum
Carbon chain extension
The mitochondrial fatty acid elongation pathway uses acetyl CoA as a two-carbon unit donor
The endoplasmic reticulum fatty acid elongation pathway uses malonyl-CoA as the two-carbon unit donor
The process is similar to the synthesis of palmitic acid, but the carrier of the fatty acyl group is CoASH.
Ingredients: Acetyl CoA
Acetyl CoA mitochondria → cytoplasm transfer mechanism—citric acid-pyruvate cycle
1 Palmitate = 1 Acetyl CoA 7 Malonyl CoA Condensation
Acetyl CoA is converted into malonyl CoA
key enzyme
Acetyl-CoA carboxylase (prosthetic group: biotin)
allosteric adjustment
activator
Citric acid, Isocitric acid
inhibitor
Palmityl-CoA, other long-chain fatty acyl-CoA
chemical modification regulation
inhibition
Glucagon → activates AMPK (protein kinase) → inhibits acetyl-CoA carboxylase activity
activation
Insulin → activates dephosphorylation of protein phosphatase → reactivates acetyl-CoA carboxylase
High sugar meals
Promote acetyl-CoA carboxylase protein synthesis
Palmitic acid undergoes 7 times of condensation-reduction-dehydration-reduction
Features
2 C extensions each time
palmitate synthase
Classification
Escherichia coli fatty acid synthase complex (multi-enzyme system)
Acyl Carrier Protein (ACP)
Function
fatty acyl carrier
acetyltransferase
B-ketoacyl synthase
malonyltransferase
B-ketoacyl reductase
dehydratase
enoyl reductase
Mammalian fatty acid synthase (multifunctional enzyme)
three domains
Substrate enters the condensation unit
Restore unit
Palmityl releasing unit
Structure (two important -SH functional parts)
ACP-SH (acyl carrier protein) = E1-pan-SH
E2-cysteine-SH
way
total reaction
parts
Adipose tissue
Liver—the main place where the body synthesizes fatty acids
kidney, brain, lung, breast
The synthesis of unsaturated fatty acids requires the catalysis of multiple desaturases
Fatty acid synthesis is regulated by metabolites and hormones
Metabolites regulate fatty acid synthesis by altering feedstock supply and acetyl-CoA carboxylase activity
Promote fatty acid synthesis
ATP, NADPH, Acetyl CoA
Glucose metabolism promotion
Inhibit fatty acid synthesis
Fatty acyl-CoA (allosteric inhibitor of acetyl-CoA carboxylase)
High-fat meal promotion
fat mobilization promotion
Insulin and glucagon
insulin
Stimulate protein phosphatase activity → dephosphorylation activation of acetyl CoA carboxylase → fatty acid synthesis
Promote fatty acid synthesis phosphatidic acid → fat
Increase adipose tissue lipoprotein lipase activity → Increase adipose tissue’s uptake of blood triglyceride fatty acids → Adipose tissue synthesizes fat for storage
glucagon, epinephrine, growth hormone
Increase protein kinase activity → Decrease phosphorylation activity of acetyl CoA carboxylase → Inhibit fatty acid synthesis
Inhibit triglyceride synthesis
Fatty acid synthase as a target for drug therapy
Fatty acid synthase inhibitors → slow tumor growth and reduce weight
Small intestinal mucosal cells-monoglyceride pathway